First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743.

Details

Serval ID
serval:BIB_78CBA16F62E5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743.
Journal
Annals of oncology
Author(s)
Peters S., Scherpereel A., Cornelissen R., Oulkhouir Y., Greillier L., Kaplan M.A., Talbot T., Monnet I., Hiret S., Baas P., Nowak A.K., Fujimoto N., Tsao A.S., Mansfield A.S., Popat S., Zhang X., Hu N., Balli D., Spires T., Zalcman G.
ISSN
1569-8041 (Electronic)
ISSN-L
0923-7534
Publication state
Published
Issued date
05/2022
Peer-reviewed
Oui
Volume
33
Number
5
Pages
488-499
Language
english
Notes
Publication types: Journal Article ; Randomized Controlled Trial
Publication Status: ppublish
Abstract
In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up.
Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or six cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including four-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs).
With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months [hazard ratio (95% confidence interval), 0.73 (0.61-0.87)], and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the four-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for 1 year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation.
With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.
Keywords
Adult, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Humans, Ipilimumab/adverse effects, Mesothelioma, Malignant, Nivolumab/therapeutic use, Progression-Free Survival, CTLA-4, PD-L1, dual immunotherapy, first-line, immune checkpoint inhibitors, overall survival
Pubmed
Open Access
Yes
Create date
12/02/2022 14:49
Last modification date
11/11/2022 6:39
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